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GeneReviews®
PAX6-Related Aniridia [Internet]

Mariya Moosajee 1 , Melanie Hingorani 2 , Anthony T Moore 3 4

Margaret P Adam, Holly H Ardinger, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, ACTIONS
Ghayda Mirzaa, Anne Amemiya, editors.
Cite
In: GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021.
2003 May 20 [updated 2018 Oct 18].
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PMID: 20301534 Bookshelf ID: NBK1360
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Clinical characteristics: PAX6-related aniridia occurs either as an isolated ocular abnormality or
as part of the Wilms tumor-aniridia-genital anomalies-retardation (WAGR) syndrome. Aniridia is a
Title & authors
pan ocular disorder affecting the cornea, iris, intraocular pressure (resulting in glaucoma), lens
(cataract and lens subluxation), fovea (foveal hypoplasia), and optic nerve (optic nerve coloboma
Excerpt
and hypoplasia). Individuals with aniridia characteristically show nystagmus and impaired visual
acuity (usually 20/100 - 20/200); however, milder forms of aniridia with subtle iris architecture
Sections
changes, good vision, and normal foveal structure do occur. Other ocular involvement may include
strabismus and occasionally microphthalmia. Although the severity of aniridia can vary between
and within families, little variability is usually observed in the two eyes of an affected individual. Similar articles

WAGR syndrome. The risk for Wilms tumor is 42.5%-77%; of those who develop Wilms tumor, 90% References
do so by age four years and 98% by age seven years. Genital anomalies in males can include
cryptorchidism and hypospadias (sometimes resulting in ambiguous genitalia), urethral strictures, Publication types
ureteric abnormalities, and gonadoblastoma. While females typically have normal external genitalia,
they may have uterine abnormalities and streak ovaries. Intellectual disability (defined as IQ <74) is Related information
observed in 70%; behavioral abnormalities include attention-deficit/hyperactivity disorder (ADHD),
autism spectrum disorder, anxiety, depression, and obsessive-compulsive disorder. Other
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individuals with WAGR syndrome can have normal intellect without behavioral problems. resources
Diagnosis/testing: The diagnosis of PAX6-related aniridia is established in a proband with one of
the two following clinical and molecular genetic findings:

Isolated aniridia (i.e., without systemic involvement) and a heterozygous PAX6 pathogenic
variant, ranging in size from a single nucleotide (e.g., those resulting in a nonsense, missense, or
splice site variant or single-nucleotide deletion or duplication) to a partial- or whole-gene
deletion (or in rare instances deletions telomeric to PAX6 that do not include PAX6); or

Aniridia and one or more additional findings of WAGR syndrome and a deletion of PAX6 and the
upstream adjacent gene, WT1

Management: Treatment of manifestations:

Aniridia. Correction of refractive errors, use of tinted or photochromic lenses to reduce light
sensitivity, occlusion therapy in childhood for amblyopia, use of low-vision aids. Treatment of
severe cataracts requires attention to potential complications caused by poor zonular stability.
Glaucoma: Initial treatment is usually topical anti-glaucoma medication; surgery is reserved for
eyes that do not respond to medical therapy. Ocular surface disease: medical treatment
(lubricants, mucolytics, and punctal occlusion) may help slow the progression of corneal
opacification. When corneal opacification causes significant visual reduction, penetrating
keratoplasty with limbal stem cell transplantation may be considered; however, this has a high
risk of failure and possible lifelong systemic immunosuppression to prevent rejection.

WAGR syndrome. Wilms tumor, genital anomalies, and developmental delay / intellectual
disability are managed as per standard practice.

Surveillance:

Aniridia. Monitor children younger than age eight years every four to six months for refractive
errors and detection and treatment of incipient or actual amblyopia; annual ophthalmology follow
up of all individuals to detect problems such as corneal changes, raised intraocular pressure,
and cataracts.

WAGR syndrome. Children with aniridia and a WT1 deletion require renal ultrasound
examinations every three months and follow up by a pediatric oncologist until age eight years.
Because of the increased risk for renal impairment in WAGR syndrome (especially in those with
bilateral Wilms tumor), lifelong evaluation of renal function is recommended. Developmental
progress and educational needs require regular monitoring. Behavioral assessment for anxiety,
ADHD, and aggressive or self-injurious behavior as needed.

Agents/circumstances to avoid: Intraocular surgery may increase the likelihood of (or exacerbate
existing) keratopathy; repeated intraocular surgery predisposes to severe aniridic fibrosis
syndrome.

Evaluation of relatives at risk: Early clarification of the genetic status of infants who are offspring or
sibs of an individual with PAX6-related isolated aniridia (by either an eye examination or molecular
genetic testing for the PAX6 variant in the family) is recommended in order to identify those who
would benefit from prompt treatment and surveillance of complications of aniridia.

Genetic counseling: Isolated aniridia and WAGR syndrome are inherited in an autosomal dominant
manner.

Isolated aniridia. ~70% of individuals have an affected parent; ~30% have a de novo PAX6
pathogenic variant or deletion of a regulatory region controlling PAX6 expression. Each child of
an individual with isolated aniridia has a 50% chance of inheriting the causative genetic
alteration and developing aniridia. In rare instances of mosaicism for the PAX6 pathogenic
variant in the proband, the risk to offspring may be lower.

WAGR syndrome is associated with contiguous-gene deletions including PAX6 and WT1. If the
proband has a de novo contiguous-gene deletion and neither parent has evidence of mosaicism
for the deletion, the risk to sibs is no greater than that in the general population.

When the PAX6 genetic alteration in a family is known, prenatal testing for a pregnancy at
increased risk and preimplantation genetic testing are possible.

Copyright © 1993-2021, University of Washington, Seattle. GeneReviews is a registered trademark of the

University of Washington, Seattle. All rights reserved.

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References
1. Abouzeid H, Youssef MA, ElShakankiri N, Hauser P, Munier FL, Schorderet DF. PAX6 aniridia
and interhemispheric brain anomalies. Mol Vis. 2009;15:2074–83. - PMC - PubMed
2. Aggarwal S, Jinda W, Limwongse C, Atchaneeyasakul LO, Phadke SR. Run-on mutation in the
PAX6 gene and chorioretinal degeneration in autosomal dominant aniridia. Mol Vis.
2011;17:1305–9. - PMC - PubMed
3. Ansari M, Rainger J, Hanson IM, Williamson KA, Sharkey F, Harewood L, Sandilands A,
Clayton-Smith J, Dollfus H, Bitoun P, Meire F, Fantes J, Franco B, Lorenz B, Taylor DS, Stewart
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Fenzy M, Prieur F, Temple IK, Lachlan KL, Damante G, Morrison DA, van Heyningen V,
FitzPatrick DR. Genetic analysis of 'PAX6-negative' individuals with aniridia or Gillespie
syndrome. PLoS One. 2016;11:e0153757. - PMC - PubMed
4. Aradhya S, Lewis R, Bonaga T, Nwokekeh N, Stafford A, Boggs B, Hruska K, Smaoui N,
Compton JG, Richard G, Suchy S. Exon-level array CGH in a large clinical cohort
demonstrates increased sensitivity of diagnostic testing for Mendelian disorders. Genet Med.
2012;14:594–603. - PubMed
5. Arroyave CP, Scott IU, Gedde SJ, Parrish RK, 2nd, Feuer WJ. Use of glaucoma drainage
devices in the management of glaucoma associated with aniridia. Am J Ophthalmol.
2003;135:155–9. - PubMed

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